pediatric reporting of adult-onset genomic results

Conditions: Hereditary Breast and Ovarian Cancer Syndrome; Lynch Syndrome; Familial Hypercholesterolemia

Summary: the investigators will conduct a longitudinal, mixed-methods cohort study to assess primary and secondary psychosocial outcomes among 705 mycode pediatric participants and their parents, and health behaviors of parents whose children receive an adult- or pediatric-onset genomic result. data will be gathered via quantitative surveys using validated measures of distress, family functioning, quality of life, body image, perceived cancer/heart disease risk, genetic counseling satisfaction, genomics knowledge, and adjustment to genetic information; qualitative interviews with adolescents and parents; and electronic health records review of parents' cascade testing uptake and initiation of risk reduction behaviors. the investigators will also conduct empirical and theoretical legal research to examine the loss of chance doctrine and its applicability to genomic research.

the investigators propose a longitudinal, observational cohort study using mixed methods to compare change in psychosocial outcomes and health behaviors among three study groups of pediatric mycode participants and their parents: 1. group 1 - those with a pathogenic variant in a gene associated with adult onset of disease (n=17 adolescents, 50 parents) 2. group 2 - those with a pathogenic variant in a gene associated with pediatric onset of disease or with risk reduction interventions that begin in childhood (n=53 adolescents, 160 parents) 3. group 3 - those who do not receive a genomic result (n=105 adolescents, 320 parents) the investigators will use the current existing mycode list of actionable genes designated as actionable by the american college of medical genetics and genomics. parents of pediatric mycode participants will be offered the opportunity to participate in the study prior to learning to which group they belong. consistent with geisinger policy, children ages 7-17 will be asked to give assent to participate. if a child does not want to assent to participate, he or she will not be enrolled into the study (regardless of their parents' preference regarding enrollment). parents of children who do not give assent will be ineligible to participate. parents who decline participation when their child is suspected to have a pathogenic adult-onset result will have their child's sample held for clinical confirmation until the child reaches age 18 years. parents who decline participation when their child is suspected to have a pathogenic pediatric-onset result will proceed to clinical confirmation of the result and, if confirmed, follow the established clinical return procedure. this recruitment approach is consistent with the mycode philosophy of notifying participants of actionable findings. parent-participants will be asked to assess psychosocial outcomes for themselves and for their children. consistent with co-investigator angela bradbury's research on the experience of adolescent girls from families at increased risk for breast cancer, pediatric participants ages 11-17 years at enrollment (i.e., adolescents) will also participate in quantitative surveys and qualitative interviews. psychosocial variables such as anxiety and depression will be assessed among parents and adolescents at enrollment (t1), after which those suspected of having a pathogenic variant will proceed to clinical confirmation of that variant. those whose variant is confirmed clinically as pathogenic or likely pathogenic will then be scheduled for a disclosure appointment. these appointments will be conducted by a genetic counselor and psychologist, who will perform psychosocial assessment, conduct therapeutic consults as needed, and conduct periodic psychosocial assessments of adolescent participants with adult-onset results. participants with suspected pathogenic variants that are not confirmed clinically and participants without a suspected pathogenic variant will be scheduled for a study visit to notify them of their group status and remind them to follow up with their pediatrician if they have significant personal or family history of cancer or heart disease. validated surveys will be used to measure outcomes in each study group at 1 month (t3), 6 months (t4) and 12 months (t5) post-disclosure visit. the investigators will conduct qualitative interviews with a subset of at least 45 participants in each of the two study groups who receive a genomic result to better understand the lived experience of adolescents with an actionable genomic finding and their parents. data collection will continue after the grant funding ends because of geisinger research division's commitment to following the study cohort. to address the legal specific aim, dr. wagner will lead the study team's legal experts in examining and monitoring the loss of chance doctrine in medical malpractice cases in federal and state courts across the united states and in monitoring legislative developments relating to the loss of chance doctrine as it applies to returning adult-onset genomic results to children.

Eligibility criteria:
inclusion criteria: * any pediatric mycode participant (ages 0-17) or * parent of a pediatric mycode participant who has given assent to participate in this study. exclusion criteria: * individuals who have already had genetic counseling for any of the actionable target conditions as part of their routine clinical care. * individuals who have already had genetic counseling for any of the actionable target conditions through their participation in another research study.

Keywords: adult-onset pediatric genomic genetic